IL257282A - Pyrazole pyrimidine derivative and uses thereof - Google Patents
Pyrazole pyrimidine derivative and uses thereofInfo
- Publication number
- IL257282A IL257282A IL257282A IL25728218A IL257282A IL 257282 A IL257282 A IL 257282A IL 257282 A IL257282 A IL 257282A IL 25728218 A IL25728218 A IL 25728218A IL 257282 A IL257282 A IL 257282A
- Authority
- IL
- Israel
- Prior art keywords
- compound
- pharmaceutically acceptable
- stereoisomer
- acceptable salt
- straight
- Prior art date
Links
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/08—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing alicyclic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Description
- 100 - 257282/3 2-(4-AMINOCYCLOHEXYLAMINO)-4-(PYRAZOL-4-YL)PYRIMIDINE ( 4 ) 4 ( 4) 2 COMPOUNDS Filing Date 04 08 2016 FIELD AND BACKGROUND OF THE INVENTION The present invention provides pyrazole pyrimidine derivatives and uses thereof m methods of treating malignant disease and disorders and methods for treating inflammatory diseases and disorders.
BACKGROUND The casein kinase 1 family (CKI, or CKI) are serine/threonine kinases with six members (isoforms) in humans: a, yl, y2, y3, 8 and£. They differ in length and sequence of the N-terminal (9- 76 amino acids) and especially the C-terminal (24- 200 amino acids) non-catalytic domain (Schittek and Sinnberg, Molecular Cancer 2014, 13:231).
CK18 and CK1£ are 98% identical in their kinase domain and 53% identical in their C-terminal regulatory domain (Fish KJ et al. J Biol Chem 1995, 270:14875- 14883). Whereas, there is some redundancy with respect to CKI substrate phosphorylation, most CKI isoforms have distinct biological roles. The wide range of CKI substrates shows that the CKI family members are involved in multiple cellular processes, from regulation of membrane trafficking, cytokinesis, vesicular transport, ribosome biogenesis, DNA repair, signal transduction pathways, apoptosis and in the circadian rhythm (Knippschild U et al. Cell Signal 2005, 17:675-689; Cheong JK and Virshup DM. Int J Biochem Cell Biol 2011, 43:465-469; Zemp I, et al. J Cell Sci 2014, 127:1242-1253).
CKla plays a role in the mitotic spindle formation during cell division and in DNA repair mechanisms and participates in RNA metabolism (Knippschild U et al. Cell Signal 2005, 17:675-689). It contributes to the activation of mTOR via sustained degradation of the endogenous mTOR inhibitor DEPTOR (Duan Set al. Mol Cell 2011, 44:317-324). 257282/2 WO 2015/058140 describes polycyclic inhibitors of cyclin dependent kinase 7 (CDK7).7
Claims (40)
1. A compound having formula (I), or a stereoisomer or pharmaceutically acceptable salt thereof: R 8 R R 3 4 N R 2 N NH R 5 R 1 N N R 7 N R 6 (I) wherein: R and R are each independently H; or straight or branched C – C alkyl, 1 2 1 8 straight or branched C – C alkoxy, straight or branched C – C acyl, or C – C 1 5 1 5 3 7 heteroaryl, each optionally substituted with at least one of halide, hydroxyl, – OC(=O)C – C alkyl, –OC – C alkyl, and C – C heteroaryl; or 1 8 1 8 3 7 R and R together with the nitrogen atom they are connected to form a 4 – 7 1 2 membered saturated, unsaturated, or aromatic ring that optionally contains at least one of N, O, NH, C=N, C=O, and SO , and is optionally substituted with at least one of 2 straight or branched C – C alkyl, C – C heteroaryl, hydroxyl, halide, and cyano; 1 5 3 7 R and R are each independently H; or straight or branched C – C alkyl, 3 4 1 8 each optionally substituted with at least one of halide, hydroxyl, C – C alkoxy, C – 1 5 3 C heteroaryl, and –OC(=O)C – C alkyl; or 7 1 8 R or R together with R and the carbon and nitrogen atoms they are each 1 2 3 connected to form a 4 – 7 membered saturated, unsaturated, or aromatic ring that optionally contains at least one of N, NH, O, C=N, C=O, and SO , and is optionally 2 substituted with at least one of straight or branched C – C alkyl, C – C heteroaryl, 1 5 3 7 hydroxyl, and halide; R and R are each independently H or halide; or straight or branched C – C 5 8 1 8 alkyl, straight or branched C – C alkenyl, or straight or branched C – C alkynyl, 2 8 2 8 each optionally substituted with at least one halide; - 101 - 257282/3 R is straight or branched C – C alkyl, straight or branched C – C alkenyl, 6 1 8 2 8 straight or branched C – C alkynyl, C – C cycloalkyl, or saturated or unsaturated 4 2 8 5 10 – 6 membered heterocyclyl, each optionally substituted with at least one of straight or branched C – C alkyl, C – C cycloalkyl, 4 – 6 membered heterocyclyl, C – C 1 8 3 7 3 7 heteroaryl, halide, hydroxyl, and C – C haloalkyl; and 1 5 R is straight or branched C – C alkyl, straight or branched C – C alkenyl, 7 1 8 2 8 or straight or branched C – C alkynyl, each substituted with at least one of C – C 2 8 3 7 cycloalkyl, 4 – 6 membered heterocyclyl, C – C heteroaryl, halide, hydroxyl, and C 3 7 1 – C haloalkyl. 5
2. The compound or stereoisomer or pharmaceutically acceptable salt according to claim 1, wherein R and R are each independently H; or straight or 1 2 branched C – C alkyl, each optionally substituted with at least one of halide, C – C 1 8 3 7 heteroaryl, hydroxyl, –OC(=O)C – C alkyl, and –OC – C alkyl. 1 8 1 8
3. The compound or stereoisomer or pharmaceutically acceptable salt according to claim 1, wherein R and R are each independently H; or straight or 1 2 branched C – C alkoxy, each optionally substituted with at least one of halide, 1 5 hydroxyl, and –OC(=O)C – C alkyl. 1 8
4. The compound or stereoisomer or pharmaceutically acceptable salt according to claim 1, wherein R and R are each independently H or C – C acyl 1 2 1 5 optionally substituted with at least one of halide, hydroxyl, –OC(=O)C – C alkyl, 1 8 and –OC – C alkyl. 1 8
5. The compound or stereoisomer or pharmaceutically acceptable salt according to claim 1, wherein R and R are each H. 1 2
6. The compound or stereoisomer or pharmaceutically acceptable salt according to any one of the preceding claims, wherein R is H. 4
7. The compound or stereoisomer or pharmaceutically acceptable salt according to any one of the preceding claims, wherein R and R are each H. 3 4 - 102 - 257282/3
8. The compound or stereoisomer or pharmaceutically acceptable salt according to any one of the preceding claims, wherein R is H, Cl, or straight or 5 branched C – C alkyl. 1 4
9. The compound or stereoisomer or pharmaceutically acceptable salt according to any one of the preceding claims, wherein R is Cl. 5
10. The compound or stereoisomer or pharmaceutically acceptable salt according to any one of the preceding claims, wherein R is H, Cl, or straight or 8 branched C – C alkyl. 1 4
11. The compound or stereoisomer or pharmaceutically acceptable salt according to any one of the preceding claims, wherein R is H. 8
12. The compound or stereoisomer or pharmaceutically acceptable salt according to any one of the preceding claims, wherein one of R and R is H. 5 8
13. The compound or stereoisomer or pharmaceutically acceptable salt according to any one of the preceding claims, wherein at least one of R and R is H. 1 2
14. The compound or stereoisomer or pharmaceutically acceptable salt according to any one of the preceding claims, wherein R is straight or branched C – 6 1 C alkyl, C – C cycloalkyl, or saturated or unsaturated 4 – 6 membered 8 5 10 heterocyclyl; and R is straight or branched C – C alkyl substituted with at least one 7 1 8 of C – C cycloalkyl, 4 – 6 membered heterocyclyl, C – C heteroaryl, halide, 3 7 3 7 hydroxyl, and C – C haloalkyl. 1 5
15. The compound or stereoisomer or pharmaceutically acceptable salt according to any one of the preceding claims, wherein R is straight or branched C – 6 1 C alkyl, C – C cycloalkyl, or 4 – 6 membered saturated heterocyclyl. 8 5 10
16. The compound or stereoisomer or pharmaceutically acceptable salt according to any one of the preceding claims, wherein R is straight C – C alkyl. 6 1 8
17. The compound or stereoisomer or pharmaceutically acceptable salt according to any one of the preceding claims, wherein R is straight or branched C – 7 1 C alkyl substituted by at least one of C – C cycloalkyl and hydroxyl. 8 3 7 - 103 - 257282/3
18. The compound or stereoisomer or pharmaceutically acceptable salt according to any one of the preceding claims, wherein R is straight or branched C – 6 1 C alkyl, or saturated , unsaturated, or aromatic 4 – 6 membered heterocyclyl, each 8 optionally substituted with at least one of straight or branched C – C alkyl, C – C 1 8 3 7 cycloalkyl, halide, hydroxyl, and CF . 3
19. The compound or stereoisomer or pharmaceutically acceptable salt according to any one of the preceding claims, wherein R is straight or branched C – 7 1 C alkyl substituted with at least one C – C cycloalkyl. 8 3 7
20. The compound or stereoisomer or pharmaceutically acceptable salt according to any one of the preceding claims, wherein R is straight or branched C – 7 1 C alkyl substituted with C – C cycloalkyl. 8 3 7
21. The compound or stereoisomer or pharmaceutically acceptable salt according to any one of the preceding claims, wherein R and R together with the 1 2 nitrogen atom they are connected to form a 4 – 7 membered saturated ring optionally containing at least one of N, O, NH, C=N, C=O, and SO ; and optionally substituted 2 with at least one of straight or branched C – C alkyl, hydroxyl, halide, and cyano. 1 5
22. The compound or stereoisomer or pharmaceutically acceptable salt according to any one of the preceding claims, wherein R and R together with the 1 2 nitrogen atom they are connected to form a 4 – 7 membered saturated ring.
23. The compound or stereoisomer or pharmaceutically acceptable salt according to any one of the preceding claims, wherein R and R together with the 1 2 nitrogen atom they are connected to form a 4 – 7 membered saturated ring containing at least one of N and O.
24. The compound or stereoisomer or pharmaceutically acceptable salt according to any one of the preceding claims, wherein R and R together with the 1 2 nitrogen atom they are connected to form a 4 – 7 membered aromatic ring optionally containing at least one of N and O.
25. The compound or stereoisomer or pharmaceutically acceptable salt according to any one of the preceding claims, wherein R or R together with R and 1 2 3 - 104 - 257282/3 the carbon and nitrogen atoms they are connected to form a 4 – 7 membered saturated ring that optionally contains at least one of N, NH, O, C=O, and SO , and is 2 optionally substituted with at least one of straight or branched C – C alkyl, hydroxyl, 1 5 and halide.
26. The compound or stereoisomer or pharmaceutically acceptable salt according to any one of the preceding claims, wherein R or R together with R and 1 2 3 the carbon and nitrogen atoms they are connected to form a 4 – 7 membered saturated ring that contains at least one of NH, O, and C=O.
27. A compound selected from: A14 , A29-1 , A27 , A28 , A36 , A39 , A29 , - 105 - 257282/3 A19-4 , A35 , A41 , A42 , A43 , A46 , A38 , A45 , A19 , A26 , A47 , - 106 - 257282/3 A48 , A49 , A50 , A51 , A52 , A53 , A58 , A59 , A56 , A57 , A30-1 , - 107 - 257282/3 A30-2 , A60 , A64 , A65 , A68 , A71 , A74 , A75 , A76 , A80 , - 108 - 257282/3 A81 , A82 , A83 , A87 , A91 , A94 , A95 , A96 , A86 , and - 109 - 257282/3 A85 ; and pharmaceutically acceptable salts.
28. The compound according to claim 27, wherein the compound is or a pharmaceutically acceptable salt thereof.
29. A pharmaceutical composition comprising the compound or stereoisomer or pharmaceutically acceptable salt according to any one of claims 1 to 28.
30. A compound or stereoisomer or pharmaceutically acceptable salt according to any one of claims 1 to 28 for use in therapy.
31. A compound or stereoisomer or pharmaceutically acceptable salt according to any one of claims 1 to28 for use in inducing antitumor response.
32. The compound or stereoisomer or pharmaceutically acceptable salt for use according to claim 31, wherein said antitumor response comprises cancer immunotherapy response.
33. A compound or stereoisomer or pharmaceutically acceptable salt according to any one of claims 1 to 28 for use in the treatment of a condition, symptom or disease associated with a malignant condition.
34. The compound or stereoisomer or pharmaceutically acceptable salt for use according to claim 33, wherein said malignant condition is cancer.
35. The compound or stereoisomer or pharmaceutically acceptable salt for use according to claim 33, wherein said malignant condition is selected from hematological malignancies, multiple myeloma, myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), melanoma, ER-negative breast cancer, diffuse large - 110 - 257282/3 B cell lymphoma (DLBCL), chronic myelogenous leukemia (CML), chronic lymphocytic leukemia (CLL), and head and neck cancer.
36. The compound or stereoisomer or pharmaceutically acceptable salt for use according to claim 34, wherein said cancer has WT p53.
37. A compound or stereoisomer or pharmaceutically acceptable salt according to any one of claims 1 to 28 for use in the treatment of cancer having WT p53, wherein said WT p53 is a biomarker for said compound efficacy.
38. The compound or stereoisomer or pharmaceutically acceptable salt for use according to claim 34, wherein said cancer is selected from multiple myeloma, leukemia, malignant melanoma, breast cancer, prostate cancer, and colorectal cancer.
39. The compound or stereoisomer or pharmaceutically acceptable salt for use according to any one of claims 33 to 38 in further inducing cancer immunotherapy response.
40. A compound or stereoisomer or pharmaceutically acceptable salt according to any one of claims 1 to 28 for use in the treatment of an inflammatory or immune related disorder. Dr. Shlomo Cohen & Co. Law Offices 5 Kineret Street Bnei Brak 5126237 Tel. 03 - 527 1919 257282/2 WO 2017/021969 PCT/IL2016/050852 - 1 - PYRAZOLE PYRIMIDINE DERIVATIVE AND USES THEREOF A2-(4-AMINOCYCLOHEXYLAMINO)-4-PYRAZOL-4-YLPYRIMIDINE COMPOUNDS TECHNOLOGICAL
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201562200846P | 2015-08-04 | 2015-08-04 | |
| US201562268750P | 2015-12-17 | 2015-12-17 | |
| PCT/IL2016/050852 WO2017021969A1 (en) | 2015-08-04 | 2016-08-04 | Pyrazole pyrimidine derivative and uses thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IL257282A true IL257282A (en) | 2018-03-29 |
| IL257282B IL257282B (en) | 2021-06-30 |
Family
ID=56738143
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL257282A IL257282B (en) | 2015-08-04 | 2018-01-31 | 2-(4-aminocyclohexylamino)-4-(pyrazol-4-yl)pyrimidine compounds |
Country Status (23)
| Country | Link |
|---|---|
| US (4) | US10376511B2 (en) |
| EP (1) | EP3331877B1 (en) |
| JP (1) | JP7083309B2 (en) |
| KR (1) | KR102698366B1 (en) |
| CN (1) | CN108137562B (en) |
| AU (2) | AU2016304464B2 (en) |
| CA (1) | CA2994644A1 (en) |
| CY (1) | CY1124898T1 (en) |
| DK (1) | DK3331877T3 (en) |
| ES (1) | ES2901349T3 (en) |
| HR (1) | HRP20211949T1 (en) |
| HU (1) | HUE057607T2 (en) |
| IL (1) | IL257282B (en) |
| LT (1) | LT3331877T (en) |
| MX (1) | MX384172B (en) |
| PL (1) | PL3331877T3 (en) |
| PT (1) | PT3331877T (en) |
| RS (1) | RS62728B1 (en) |
| RU (1) | RU2735522C2 (en) |
| SI (1) | SI3331877T1 (en) |
| SM (1) | SMT202100720T1 (en) |
| WO (1) | WO2017021969A1 (en) |
| ZA (1) | ZA201800671B (en) |
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| HRP20211949T1 (en) * | 2015-08-04 | 2022-03-18 | Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd. | Pyrazole pyrimidine derivative and uses thereof |
| NZ755447A (en) | 2017-02-01 | 2023-05-26 | Yissum Res Dev Co Of Hebrew Univ Jerusalem Ltd | N1 -(4-(5-(cyclopropylmethyl)-1 -methyl-1 h-pyrazol-4-yl)pyridin-2-yl)cyclohexane-1,4-diamine derivatives and related compounds as ck1 and/or iraki inhibitors for treating cancer |
| JOP20180011A1 (en) | 2017-02-16 | 2019-01-30 | Gilead Sciences Inc | Perulo derivatives [1, 2-b] pyridazine |
| AU2019219678A1 (en) * | 2018-02-08 | 2020-08-27 | Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd. | Heteroaryl compounds, pharmaceutical compositions thereof, and their therapeutic use |
| TWI721483B (en) | 2018-07-13 | 2021-03-11 | 美商基利科學股份有限公司 | Pyrrolo[1,2-b]pyridazine derivatives |
| US11066404B2 (en) | 2018-10-11 | 2021-07-20 | Incyte Corporation | Dihydropyrido[2,3-d]pyrimidinone compounds as CDK2 inhibitors |
| US11384083B2 (en) | 2019-02-15 | 2022-07-12 | Incyte Corporation | Substituted spiro[cyclopropane-1,5′-pyrrolo[2,3-d]pyrimidin]-6′(7′h)-ones as CDK2 inhibitors |
| US11472791B2 (en) | 2019-03-05 | 2022-10-18 | Incyte Corporation | Pyrazolyl pyrimidinylamine compounds as CDK2 inhibitors |
| WO2020205560A1 (en) | 2019-03-29 | 2020-10-08 | Incyte Corporation | Sulfonylamide compounds as cdk2 inhibitors |
| US11447494B2 (en) | 2019-05-01 | 2022-09-20 | Incyte Corporation | Tricyclic amine compounds as CDK2 inhibitors |
| US11440914B2 (en) | 2019-05-01 | 2022-09-13 | Incyte Corporation | Tricyclic amine compounds as CDK2 inhibitors |
| CN114423752B (en) * | 2019-06-03 | 2025-06-24 | 耶路撒冷希伯来大学伊萨姆研究发展公司 | Non-hygroscopic crystalline salt of pyrazole compound and pharmaceutical composition and use thereof |
| WO2021000957A1 (en) * | 2019-07-04 | 2021-01-07 | 北京国鸿生物医药科技有限公司 | Heterocyclic compound and pharmaceutical composition thereof and use thereof |
| MX2022001940A (en) | 2019-08-14 | 2022-05-10 | Incyte Corp | IMIDAZOLIL PYRIMIDINILAMINE COMPOUNDS AS CDK2 INHIBITORS. |
| CN119930610A (en) | 2019-10-11 | 2025-05-06 | 因赛特公司 | Dicyclomine as a CDK2 inhibitor |
| US20230047732A1 (en) * | 2020-01-13 | 2023-02-16 | Biotheryx, Inc. | Pyrazolylpyrimidines and use thereof |
| WO2021155050A1 (en) * | 2020-01-29 | 2021-08-05 | Biotheryx, Inc. | Kinase modulators, pharmaceutical compositions, and therapeutic applications |
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| AU2022242818A1 (en) * | 2021-03-24 | 2023-10-05 | Yissum Research Development Company Of The Hebrew University Of Jerusalem, Ltd. | Pyrazolylpyrimidines for treating malignant solid tumor |
| US11981671B2 (en) | 2021-06-21 | 2024-05-14 | Incyte Corporation | Bicyclic pyrazolyl amines as CDK2 inhibitors |
| US11752151B2 (en) * | 2021-07-12 | 2023-09-12 | Buddhist Tzu Chi Medical Foundation | Method for enhancing hair growth |
| US20230053307A1 (en) * | 2021-07-19 | 2023-02-16 | Buddhist Tzu Chi Medical Foundation | Method for preventing or treating skin disorders and conditions |
| US11976073B2 (en) | 2021-12-10 | 2024-05-07 | Incyte Corporation | Bicyclic amines as CDK2 inhibitors |
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| US10047070B2 (en) * | 2013-10-18 | 2018-08-14 | Dana-Farber Cancer Institute, Inc. | Polycyclic inhibitors of cyclin-dependent kinase 7 (CDK7) |
| HRP20211949T1 (en) * | 2015-08-04 | 2022-03-18 | Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd. | Pyrazole pyrimidine derivative and uses thereof |
| NZ755447A (en) * | 2017-02-01 | 2023-05-26 | Yissum Res Dev Co Of Hebrew Univ Jerusalem Ltd | N1 -(4-(5-(cyclopropylmethyl)-1 -methyl-1 h-pyrazol-4-yl)pyridin-2-yl)cyclohexane-1,4-diamine derivatives and related compounds as ck1 and/or iraki inhibitors for treating cancer |
| AU2019219678A1 (en) | 2018-02-08 | 2020-08-27 | Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd. | Heteroaryl compounds, pharmaceutical compositions thereof, and their therapeutic use |
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